CAS 439239-90-4|Lasmiditan

Introduction：Basic information about CAS 439239-90-4|Lasmiditan, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Lasmiditan BiologicalActivity
3. Chemical & Physical Properties
4. Safety Information
5. Customs
6. Synonyms

Common Name	Lasmiditan
CAS Number	439239-90-4	Molecular Weight	377.360
Density	1.4±0.1 g/cm3	Boiling Point	433.3±45.0 °C at 760 mmHg
Molecular Formula	C₁₉H₁₈F₃N₃O₂	Melting Point	/
MSDS	/	Flash Point	215.9±28.7 °C

Names

Name	2,4,6-trifluoro-N-[6-(1-methylpiperidine-4-carbonyl)pyridin-2-yl]benzamide
Synonym	More Synonyms

Lasmiditan BiologicalActivity

Description	Lasmiditan (COL-144; LY573144) is a high-affinity, highly selective 5-HT1F receptor agonist(Ki=2.1 nM), compared with Ki of 1043 nM and 1357 nM at the 5-HT(1B) and 5-HT(1D) receptors, respectively.IC50 value: 2.1 nM (Ki, 5-HT1F); >1000 nM (Ki, 5-HT1B/5-HT1D) [1]Target: 5-HT1F receptorin vitro: In vitro binding studies Lasmiditan showed a K(i) value of 2.21 nM at the 5-HT(1F) receptor, compared with K(i) values of 1043 nM and 1357 nM at the 5-HT(1B) and 5-HT(1D) receptors, respectively, a selectivity ratio greater than 470-fold. Lasmiditan showed higher selectivity for the 5-HT(1F) receptor relative to other 5-HT(1) receptor subtypes than the first generation 5-HT(1F) receptor agonist LY334370. Unlike the 5-HT(1B/1D) receptor agonist sumatriptan, lasmiditan did not contract rabbit saphenous vein rings, a surrogate assay for human coronary artery constriction, at concentrations up to 100 μM [1].in vivo: In two rodent models of migraine, oral administration of lasmiditan potently inhibited markers associated with electrical stimulation of the trigeminal ganglion (dural plasma protein extravasation, and induction of the immediate early gene c-Fos in the trigeminal nucleus caudalis) [1]. Two RCTs in the phase II development of lasmiditan was reviewed. In the intravenous placebo-controlled RCT, lasmiditan doses of 2.5-45 mg were used, and there was a linear association between headache relief (HR) rates and dose levels (P < 0.02). For lasmiditan 20 mg, HR was 64 % and for placebo it was 45 % (NS). In the oral placebo-controlled RCT, lasmiditan doses of 50, 100, 200 and 400 mg were used. For HR, all doses of lasmiditan were superior to placebo (P < 0.05). For lasmiditan 400 mg, HR was 64 % and it was 25 % for placebo. Adverse events (AEs) emerging from the treatment were reported by 22 % of the patients receiving placebo and by 65, 73, 87 and 87 % of patients receiving 50, 100, 200 and 400 mg, respectively [2].
Related Catalog	Signaling Pathways >>GPCR/G Protein >>5-HT ReceptorSignaling Pathways >>Neuronal Signaling >>5-HT ReceptorResearch Areas >>Neurological Disease
References	[1]. Nelson DL, et al. Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmiditan. Cephalalgia. 2010 Oct;30(10):1159-69. [2]. Tfelt-Hansen PC, et al. The 5-HT1F receptor agonist lasmiditan as a potential treatment of migraine attacks: a review of two placebo-controlled phase II trials. J Headache Pain. 2012 Jun;13(4):271-5.

Description

Lasmiditan (COL-144; LY573144) is a high-affinity, highly selective 5-HT1F receptor agonist(Ki=2.1 nM), compared with Ki of 1043 nM and 1357 nM at the 5-HT(1B) and 5-HT(1D) receptors, respectively.IC50 value: 2.1 nM (Ki, 5-HT1F); >1000 nM (Ki, 5-HT1B/5-HT1D) [1]Target: 5-HT1F receptorin vitro: In vitro binding studies Lasmiditan showed a K(i) value of 2.21 nM at the 5-HT(1F) receptor, compared with K(i) values of 1043 nM and 1357 nM at the 5-HT(1B) and 5-HT(1D) receptors, respectively, a selectivity ratio greater than 470-fold. Lasmiditan showed higher selectivity for the 5-HT(1F) receptor relative to other 5-HT(1) receptor subtypes than the first generation 5-HT(1F) receptor agonist LY334370. Unlike the 5-HT(1B/1D) receptor agonist sumatriptan, lasmiditan did not contract rabbit saphenous vein rings, a surrogate assay for human coronary artery constriction, at concentrations up to 100 μM [1].in vivo: In two rodent models of migraine, oral administration of lasmiditan potently inhibited markers associated with electrical stimulation of the trigeminal ganglion (dural plasma protein extravasation, and induction of the immediate early gene c-Fos in the trigeminal nucleus caudalis) [1]. Two RCTs in the phase II development of lasmiditan was reviewed. In the intravenous placebo-controlled RCT, lasmiditan doses of 2.5-45 mg were used, and there was a linear association between headache relief (HR) rates and dose levels (P < 0.02). For lasmiditan 20 mg, HR was 64 % and for placebo it was 45 % (NS). In the oral placebo-controlled RCT, lasmiditan doses of 50, 100, 200 and 400 mg were used. For HR, all doses of lasmiditan were superior to placebo (P < 0.05). For lasmiditan 400 mg, HR was 64 % and it was 25 % for placebo. Adverse events (AEs) emerging from the treatment were reported by 22 % of the patients receiving placebo and by 65, 73, 87 and 87 % of patients receiving 50, 100, 200 and 400 mg, respectively [2].

Related Catalog

Signaling Pathways >>GPCR/G Protein >>5-HT ReceptorSignaling Pathways >>Neuronal Signaling >>5-HT ReceptorResearch Areas >>Neurological Disease

References

[1]. Nelson DL, et al. Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmiditan. Cephalalgia. 2010 Oct;30(10):1159-69.

[2]. Tfelt-Hansen PC, et al. The 5-HT1F receptor agonist lasmiditan as a potential treatment of migraine attacks: a review of two placebo-controlled phase II trials. J Headache Pain. 2012 Jun;13(4):271-5.

Chemical & Physical Properties

Density	1.4±0.1 g/cm3
Boiling Point	433.3±45.0 °C at 760 mmHg
Molecular Formula	C₁₉H₁₈F₃N₃O₂
Molecular Weight	377.360
Flash Point	215.9±28.7 °C
Exact Mass	377.135101
PSA	62.30000
LogP	1.90
Vapour Pressure	0.0±1.0 mmHg at 25°C
Index of Refraction	1.585
InChIKey	XEDHVZKDSYZQBF-UHFFFAOYSA-N
SMILES	CN1CCC(C(=O)c2cccc(NC(=O)c3c(F)cc(F)cc3F)n2)CC1
Storage condition	2-8℃

Safety Information

HS Code	2933990090

Customs

HS Code	2933990090
Summary	2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Synonyms

COL-144

2,4,6-trifluoro-N-[6-(1-methyl-piperidin-4-ylcarbonyl)-pyridin-2-yl]-benzamide

2,4,6-Trifluoro-N-(6-(1-methylpiperidine-4-carbonyl)pyridin-2-yl)benzamide

Lasmiditan [INN]

2,4,6-trifluoro-N-{6-[(1-methylpiperidin-4-yl)carbonyl]pyridin-2-yl}benzamide

2,4,6-trifluoro-N-[6-(1-methyl-piperidin-4-ylcarbonyl)-pyridine-2-yl]-benzamide

2,4,6-Trifluoro-N-{6-[(1-methyl-4-piperidinyl)carbonyl]-2-pyridinyl}benzamide

2,4,6-trifluoro-N-(6-(1-methylpiperidine-4-carbonyl)pyridine-2-yl)benzamide

Lasmiditan (USAN/INN)

lasmitidan

Lasmiditan

Benzamide, 2,4,6-trifluoro-N-[6-[(1-methyl-4-piperidinyl)carbonyl]-2-pyridinyl]-

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